Zscan10 – maintainance of a multipotent progenitor cell population

Zscan10 (previously known as Zfp206) is a 14 zinc finger transcription factor (ZF-TF) of the C2H2 ZF-TF subfamily with a N-terminal SCAN domain. Zscan10 had been attributed a role as a pluripotency factor in embryonic stem cells based on its interaction with Oct4 and Sox2 in in vitro assays.

To obtain better insights into the potential roles of Zscan10 mice containing a mutation in the Zscan10 gene were analysed in the phenotypic screen of the German Mouse Clinic. Homozygous mutants exhibited phenotypic differences from wild type litter mates in several screens. Mice homozygous for a Zscan10 mutation exhibit reduced weight while the relationship between body fat content and lean mass was not different between mutant and wild type mice. In DXA analysis a significantly decreased bone mineral content (BMC) and bone content was observed in female mutants. The tibia length was significantly reduced in female mice. The clinical-chemical and hematological screen detected several changes indicating effects of the Zscan10 mutation on renal function as well as platelet number and morphology. Differences were also observed in the behavior. Female mutant mice showed increased locomotor activity (total distance travelled) and increased locomotor speed in the open field and entered the center more frequently while male mutant mice showed the opposite effect. Male mutant mice also exhibited increased PPI and female mutants exhibited an increase in acoustic startle reactivity at higher sound pressure levels. During the SHIRPA test increased occurrence of urination was detected for two thirds of the mutant cohort, compared to only one third of the wild type mice. Furthermore, mild hypoplasia in the spleen, heart and long bones and phenocopy an eye malformation previously described for Sox2 hypomorphs were detected.

Because Zscan10 was known to interact with known pluripotency markers like Oct4 and Sox2 in embryonic stem cells a potential crucial role of Zscan10 in early mouse development was assumed. The authors propose – based on a more refined expression pattern by SISH and the pleiotropic phenotype observed in Zscan10 mutants – that Zscan10 could play a role in regulating the availability of progenitor cells during mouse embryonic development and adulthood. In the case of Zscan10 hypomorphic or loss-of-function mutations the number of progenitors might be reduced, either by a decrease in progenitor cell division or by premature terminal differentiation causing an overall reduction in cell mass of a variety of target tissues namely eye, heart, long bones and spleen.